Regulation of gene transcription is the primary process by which a cell controls the appropriate expression of the multitude of genes necessary for growth and differentiation. The selective expression of genes at appropriate times is highly specialized in cells of multicellular organisms and permits the cells to perform "housekeeping" functions and respond to changes in their environment. These changes occur as a result of extracellular signals from a variety of sources such as hormones, neurotransmitters, and growth and differentiation factors.
Gene transcription is controlled by a regulator of gene transcription (RGT). RGTs act by binding to a short segment of DNA (transcription control element, TCE) located near the site of transcription initiation. Binding of an RGT to the target TCE activates transcription of the gene. RGTs contain a variety of structural motifs that, alone or in combination with one another, permit them to recognize and bind to the wide variety of TCEs. One group of RGTs have an amino acid motif known as a leucine zipper. The leucine zipper also forms dimers and has a 30-40 residue motif in which two .alpha. helices (one from each monomer) are joined together to form a short coiled-coil. The helices are held together by interactions among hydrophobic amino acid side chains (often on heptad-repeated leucines) that extend from one side of each helix. Beyond this, the helices separate, and each basic region contacts the major groove of DNA. The overall configuration resembles a clothespin (the dimer) pinching a clothesline (DNA helix). Proteins with the leucine zipper motif can also form either homodimers or heterodimers extending the specific combinations available to activate or repress expression. This strategy is sometimes discussed as combinatorial control (cf. Busch S. J. et al. (1990) Trends Genet. 6:36-40).
The leucine zipper-containing RGT, TSC-22, is rapidly and transiently induced in rodents by transforming growth factor beta (TGF; Shibanuma M. et al. (1992) J. Biol. Chem. 267: 10219-10224). TGF has a variety of biological functions and is involved particularly in cell growth and differentiation. The TSC-22 protein has been found in both the cell cytoplasm and nucleus where it is thought to regulate gene expression. Several TSC-22 homologs have been identified, and in many cases, their role in development has been confirmed. For example, the TSC-22 homolog, "shortsighted", is necessary for several developmental processes such as photoreceptor differentiation in Drosophila melanogaster. The shortsighted homolog interacts with several other known developmental factors including hedgehog, decapentaplcgic, and wingless. Two human homologs of rodent TSC-22 have been described, hDIP (Vogel P. et al. (1996) Biochim. Biophys. Acta. 1309: 200-204) and hTSC-22 (Jay P. et al. (1996) Biochem. Biophy. Res. Commun. 222: 821-826).
The discovery of a new human TSC-22 homolog and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of disorders of cell proliferation and cell signaling.